Person: Vallet Regí, María Dulce Nombre
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First Name
María Dulce Nombre
Last Name
Vallet Regí
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Inorgánica
Identifiers
47 results
Search Results
Now showing 1 - 10 of 47
Item Preventing bacterial adhesion on scaffolds for bone tissue engineering(International Journal of Bioprinting, 2016) Sánchez Salcedo, Sandra; Colilla Nieto, Montserrat; Izquierdo Barba, Isabel; Vallet Regí, María Dulce NombreBone implant infection constitutes a major sanitary concern which is associated to high morbidity and health costs. This manuscript focused on overviewing the main research efforts committed up to date to develop innovative alternatives to conventional treatments, such as those with antibiotics. These strategies mainly rely on chemical modifi-cations of the surface of biomaterials, such as providing it of zwitterionic nature, and tailoring the nanostructure surface of metal implants. These surface modifications have successfully allowed inhibition of bacterial adhesion, which is the first step to implant infection, and preventing long-term biofilm formation compared to pristine materials. These strate-gies could be easily applied to provide three-dimensional (3D) scaffolds based on bioceramics and metals, of which its manufacture using rapid prototyping techniques was reviewed. This opens the gates for the design and development of advanced 3D scaffolds for bone tissue engineering to prevent bone implant infections. Keywords: Antibacterial adhesion, biofilm formation, zwitterionic surfaces, nanostructured surfaces, rapid prototyping 3D scaffolds, bone tissue engineering.Item Effects of bleaching on osteoclast activity and their modulation by osteostatin and fibroblast growth factor 2(Journal of Colloid and Interface Science, 2016) Torres-Rodriguez, Carolina; Portolés Pérez, María Teresa; Matesanz Sancho, María Concepción; Linares, Javier; Feito Castellano, María José; Izquierdo Barba, Isabel; Esbrit, Pedro; Vallet Regí, María Dulce NombreHypothesis: Dental bleaching with H2O2 is a common daily practice in dentistry to correct discoloration of anterior teeth. The aim of this study has been to determine whether this treatment of human teeth affects growth, differentiation and activity of osteoclast-like cells, as well as the putative modulatory action of osteostatin and fibroblast growth factor 2 (FGF-2). Experiments: Previously to the in vitro assays, structural, physical-chemical and morphological features of teeth after bleaching were studied. Osteoclast-like cells were cultured on human dentin disks, pre-treated or not with 38% H2O2 bleaching gel, in the presence or absence of osteostatin (100 nM) or FGF-2 (1 ng/ml). Cell proliferation and viability, intracellular content of reactive oxygen species (ROS), pro-inflammatory cytokine (IL-6 and TNF alpha) secretion and resorption activity were evaluated. Findings: Bleaching treatment failed to affect either the structural or the chemical features of both enamel and dentin, except for slight morphological changes, increased porosity in the most superficial parts (enamel), and a moderate increase in the wettability degree. In this scenario, bleaching produced an increased osteoclast-like cell proliferation but decreased cell viability and cytokine secretion, while it augmented resorption activity on dentin. The presence of either osteostatin or FGF-2 reduced the osteoclast-like cell proliferation induced by bleaching. FGF-2 enhanced ROS content, whereas osteostatin decreased ROS but increased TNF alpha secretion. The bleaching effect on resorption activity was increased by osteostatin, but this effect was less evident with FGF-2. Conclusions: These findings further confirm the deleterious effects of tooth bleaching by affecting osteoclast growth and function as well as different modulatory actions of osteostatin and FGF-2. (C) 2015 Elsevier Inc. All rights reserved.Item Effects of 3D nanocomposite bioceramic scaffolds on the immune response(Journal of Materials Chemistry B, 2014) Cicuéndez Maroto, Mónica; Portoles, Pilar; Montes Casado, María; Izquierdo Barba, Isabel; Vallet Regí, María Dulce Nombre; Portolés Pérez, María TeresaThe interaction of new nanocomposite mesoporous glass/hydroxyapatite (MGHA) scaffolds with immune cells involved in both innate and acquired immunity has been studied in vitro as an essential aspect of their biocompatibility assessment. Since the immune response can be affected by the degradation products of bioresorbable scaffolds and scaffold surface changes, both processes have been evaluated. No alterations in proliferation and viability of RAW-264.7 macrophage-like cells were detected after culture on MGHA scaffolds which did not induce cell apoptosis. However, a slight cell size decrease and an intracellular calcium content increase were observed after contact of this cell line with MGHA scaffolds or their extracts. Although no changes in the percentages of RAW cells with low and high contents of reactive oxygen species (ROS) are observed by the treatment with 7 day extracts, this study has revealed modifications of these percentages after direct contact with scaffolds and by the treatment with 24 h extracts, related to the high reactivity/bioactivity of this MGHA nanocomposite at initial times. Furthermore, when normal fresh murine spleen cells were used as an experimental model closer to physiological conditions, no significant alterations in the activation of different immune cell subpopulations were detected in the presence of 24 h MGHA extract. MGHA scaffolds did not affect either the spontaneous apoptosis or intracellular cytokine expression (IL-2, IL-10, IFN-gamma, and TNF-alpha.) after 24 h treatment. The results obtained in the present study with murine immune cell subpopulations (macrophages, lymphocytes B, lymphocytes T and natural killer cells) support the biocompatibility of the MGHA material and suggest an adequate host tissue response to their scaffolds upon their implantation.Item Proton Environments in Biomimetic Calcium Phosphates Formed from Mesoporous Bioactive CaO-SiO2- P2O5 Glasses in vitro: Insights from Solid-State NMR(Journal of Physical Chemistry C, 2017) Mathew, Renny; Turdean-Ionescu, Claudia; Yu, Yang; Stevensson, Baltzar; Izquierdo Barba, Isabel; García Fontecha, Ana; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Eden, MattiasWhen exposed to body fluids, mesoporous bioactive glasses (MBGs) of the CaO{SiO2{P2O5 system develop a bone-bonding surface layer that initially consists of amorphous calcium phosphate(ACP), which transforms into hydroxy-carbonate apatite (HCA) with a very similar composition as bone/dentin mineral. Information from various 1H-based solid-state nuclear magnetic resonance (NMR) experiments were combined to elucidate the evolution of the proton speciations both at the MBG surface and within each ACP/HCA constituent of the biomimetic phosphate layer formed when each of three MBGs with distinct Ca, Si, and P contents was immersed in a simulated body fluid (SBF) for variable periods between 15 min and 30 days. Directly excited magic-angle-spinning (MAS) 1H NMR spectra mainly reflect the MBG component, whose surface is rich in water and silanol (SiOH) moieties. Double-quantum{single-quantum correlation 1H NMR experimentation at fast MAS revealed their interatomic proximities. The comparatively minor H species of each ACP and HCA component were probed selectively by heteronuclear 1H{31P NMR experimentation. The initially prevailing ACP phase comprises H2O and "non-apatitic" HPO2.Item Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment.(Acta Biomaterialia, 2018) Izquierdo Barba, Isabel; Santos-Ruiz, L; Becerra, J; Feito Castellano, María José; Fernandez-Villa, D; Serrano, M.C; Diaz-Gúemes, I; Fernandez-Tome, B; Enciso, S; Sanchez-Margallo, F.M; Monopoli, D; Alfonso, H; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreThe osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone. STATEMENT OF SIGNIFICANCE Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with an osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.Item Essential role of calcium phosphate heterogeneities in 2D-hexagonal and 3D-cubic SiO2-CaO-P2O5 mesoporous bioactive glasses(Chemistry of Materials, 2009) García, Ana; Cicuéndez Maroto, Mónica; Izquierdo Barba, Isabel; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreMesoporous bioactive glasses (MBGs) with a compoisition of 85SiO2-10CaO-5P2O5 (mol %) have been prepared through the evaporation-induced self-assembly (EISA) method, using P123 as a structure directing agent. For the first time, SiO2-CaO-P2O5 MBGs with identical composition and textural properties, but exhibiting different bicontinuous 3D-cubic and 2D-hexagonal structures, have been prepared. These materials allow us to discriminate the role of the structure on the bioactivity, from other parameters. To understand the role of each component on the mesostructure, local environment, and bioactive behavior, mesoporous 100SiO2, 95SiO2-5P2O5,and 90SiO2-10CaO (mol %) materials were also prepared under the same conditions. The results demonstrate that the joint presence of CaO and P2O5 results in amorphous calcium phosphate (ACP) clusters sited at the pore wall surface. This heterogeneity highly improves the bioactive behavior of these materials. In addition, the presence of ACP clusters within the silica network leads to different mesoporous structures. The mesoporous order can be tuned through a rigorous control of the solvent evaporation temperature during the mesophase formation, resulting in p6mm, p6mm/Ia3d coexistence, and Ia3d phases for 20, 30, and 40 C, respectively. Preliminary results indicate that, in the case of identical composition and textural properties, the mesoporous structure does not have influence on the apatite formation, although initial ionic exchange is slightly enhanced for 3D cubic bicontinuous structures.Item 3D scaffold with effective multidrug sequential release against bacteria biofilm(Acta Biomaterialia, 2016) García Álvarez, Rafaela; Izquierdo Barba, Isabel; Vallet Regí, María Dulce NombreBone infection is a feared complication following surgery or trauma that remains as an extremely difficult disease to deal with. So far, the outcome of therapy could be improved with the design of 3D implants, which combine the merits of osseous regeneration and local multidrug therapy so as to avoid bacterial growth, drug resistance and the feared side effects. Herein, hierarchical 3D multidrug scaffolds based on nanocomposite bioceramic and polyvinyl alcohol (PVA) prepared by rapid prototyping with an external coating of gelatin-glutaraldehyde (Gel-Glu) have been fabricated. These 3D scaffolds contain three antimicrobial agents (rifampin, levofloxacin and vancomycin), which have been localized in different compartments of the scaffold to obtain different release kinetics and more effective combined therapy. Levofloxacin was loaded into the mesopores of nanocomposite bioceramic part, vancomycin was localized into PVA biopolymer part and rifampin was loaded in the external coating of Gel-Glu. The obtained results show an early and fast release of rifampin followed by sustained and prolonged release of vancomycin and levofloxacin, respectively, which are mainly governed by the progressive in vitro degradability rate of these scaffolds. This combined therapy is able to destroy Gram-positive and Gram-negative bacteria biofilms as well as inhibit the bacteria growth; in addition, these multifunctional scaffolds exhibit excellent bioactivity as well as good biocompatibility with complete cell colonization of preosteoblast in the entire surface, ensuring good bone regeneration. These findings suggest that these hierarchical 3D multidrug scaffolds are promising candidates as platforms for local bone infection therapy.Item Amine-Functionalized Mesoporous Silica Nanoparticles: A New Nanoantibiotic for Bone Infection Treatment(Biomedical Glasses, 2018) Pedraza, Daniel; Díez, Jaime; Izquierdo Barba, Isabel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreThis manuscript reports an effective new alternative for the management of bone infection by the 5 development of an antibiotic nanocarrier able to penetrate bacterial biofilm, thus enhancing antimicrobial effectiveness. This nanosystem, also denoted as “nanoantibiotic”, consists in mesoporous silica nanoparticles (MSNs) loaded with an antimicrobial agent (levofloxacin, LEVO) 10 and externally functionalized with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (DAMO) as targeting agent. This amine functionalization provides MSNs of positive charges, which improves the affinity towards the negatively charged bacteria wall and biofilm. Physical and 15 chemical properties of the nanoantibiotic were studied using different characterization techniques, including Xray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption porosimetry, elemental chemical analysis, dynamic light scattering (DLS), zeta (� )-potential 20 and solid-state nuclear magnetic resonance (NMR). “In vial” LEVO release profiles and the in vitro antimicrobial effectiveness of the different released doses were investigated. The efficacy of the nanoantibiotic against a S. aureus biofilm was also determined, showing the practically total 25 destruction of the biofilmdue to the high penetration ability of the developed nanosystem. These findings open up promising expectations in the field of bone infection treatment.Item Concanavalin A-targeted mesoporous silica nanoparticles for infection treatment.(Acta Biomaterialia, 2019) Martínez Carmona, Marina; Izquierdo Barba, Isabel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreThe ability of bacteria to form biofilms hinders any conventional treatment for chronic infections and has serious socio-economic implications. For this purpose, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loadedantibiotic within this matrix would be desirable. Herein, we developed a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSNs) decorated with the lectin concanavalin A (ConA). The presence of ConA promotes the internalization of this nanosystem into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional treatments for infection by improving the antimicrobial efficacy and reducing side effects.Item Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model(Advanced Materials Interfaces, 2020) Moreno Zafra, Víctor Manuel; Alvarez Corchado, Elena; Izquierdo Barba, Isabel; Baeza, Alejandro; Serrano López, Juana; Vallet Regí, María Dulce NombreOne of the major concerns in the application of nanocarriers in oncology is their scarce penetration capacity in tumoral tissues, which drastically compromises the effectivity. Living organisms as cells and bacteria present the capacity to navigate autonomously following chemical gradients being able to penetrate deeply into dense tissues. In the recent years, the possibility to employ these organisms for the transportation of therapeutic agents and nanocarriers attached on their membrane or engulfed in their inner space have received huge attention. Herein, based on this principle, a new approach to deliver drug loaded nanoparticles achieving high penetration in tumoral matrices is presented. In this case, Escherichia coli (E. coli) bacteria wall is decorated with azide groups, whereas alkyne-strained groups are incorporated on the surface of mesoporous silica nanoparticles loaded with a potent cytotoxic compound, doxorubicin. Both functional groups form stable triazole bonds by click-type reaction allowing the covalent grafting of nanoparticles on living bacteria. Thus, the motility and penetration capacity of bacteria, which carried nanoparticles are evaluated in a 3D tumoral matrix model composed by a dense collagen extracellular matrix with HT1080 human fibrosarcome cells embedded. The results confirmed that bacteria are able to transport the nanoparticles crossing a thick collagen layer being able to destroy almost 80% of the tumoral cells located underneath. These findings envision a powerful strategy in nanomedicine applied for cancer treatment by Q4 allowing a homogeneous distribution of therapeutic agents in the malignancy.